EP1763355A1

EP1763355A1 - Use of composition comrising d-mannoheptulose and/or perseitol for the treatment and prevention of diseases linked to a modification of the innate immunity

Info

Publication number: EP1763355A1
Application number: EP05763732A
Authority: EP
Inventors: Antoine Piccirilli; Nathalie Piccardi; Philippe Msika; François Paul; Stéphanie BREDIF
Original assignee: Laboratoires Expanscience SA
Current assignee: Laboratoires Expanscience SA
Priority date: 2004-04-30
Filing date: 2005-04-29
Publication date: 2007-03-21
Anticipated expiration: 2025-04-29
Also published as: US7897579B2; JP4903131B2; CN1968707B; JP2007535523A; ES2769246T3; US9023810B2; WO2005115421A8; MXPA06012556A; US20080113921A1; FR2869541A1; EP1763355B1; FR2869541B1; US20110274778A1; CN1968707A; WO2005115421A1

Abstract

The invention relates to the use of a compound comprising D-mannoheptulose and/ or perseitol for producing a drug for treating and/or preventing diseases related to the modification of an innate and/or acquired immunity by increasing the production of antimicrobial peptides, preferably hBD-2 without inducing inflammatory reactions, irritation or intolerance. Said compound can also comprise a peptidic avocado extract an/or a peptidic lupin extract.

Description

Use of a composition comprising D-mannoheptulose and / or perseitol in the treatment and prevention of diseases linked to a modification of innate immunity. The present invention relates to the use of a composition comprising D-mannoheptulose and / or perseitol for the manufacture of a medicament intended for the treatment and / or prevention of diseases linked to a modification of innate immunity. All animal species are confronted daily with a large number of microorganisms, such as bacteria, fungi, parasites or viruses, which can affect their health or even their survival. Two defense systems oppose these microorganisms: a system called innate immunity, which is common to all animals, including humans, and a so-called adaptive or specific immune system which is acquired thanks to cells and mediators of l immunity after contact with the potential aggressor. A difference between innate or adaptive immune responses lies in the recognition mechanisms of the microorganisms involved. In innate immunity, the specificity of receptors is genetically determined from birth and is not variable. These receptors are expressed on cells such as certain epithelial and endothelial cells, dendritic cells, monocytes and macrophages. All the structures recognized by the receptors of innate immunity are common to very numerous microorganisms. Unlike the adaptive immune response, the mechanisms of the innate immune response (phagocytosis, antimicrobial peptides, ...) are activated from the start of the infection and almost immediately control the proliferation of pathogens that invade the host. Then the adaptive immune response takes over. Antimicrobial peptides have been found in both the plant and animal kingdoms, and more than 500 different antimicrobial peptides have been discovered from insects to humans. Antimicrobial peptides are small molecules (10 to 50 amino acids) capable of destroying a wide variety of microorganisms (Gram + and / or Gram- bacteria, fungi, viruses, transformed cells), permeabilizing their cell membrane. In addition, some of these antimicrobial peptides via chemo-attractive properties are capable of recruiting cells participating in adaptive immunity such as dendritic cells or even T lymphocytes. Many anti-microbial peptides have been demonstrated in vernix caseosa and in amniotic fluid, as well as in the skin of newborns, suggesting their key role in antimicrobial defense during childbirth, but also from the beginning of life while acquired immunity is still immature. Most organisms synthesize several types of antimicrobial peptides at the level of their different epithelia, so as to define a broad spectrum of activity. In mammals, two major classes of antimicrobial peptides, the production of which is induced upon contact with a microorganism, have been described: cathelicidins and defensins. Human cathelicidin (LL-37) was first isolated from cells in the bone marrow. LL-37 is expressed in particular in human skin, at the level of the nails, as well as at the level of the healthy and inflammatory synovial membrane, especially in patients suffering from osteoarthritis. LL-37 has a broad spectrum of activity, and appears to act in synergy with other antimicrobial peptides, in particular defensins. LL-37 also has chemo-attractive properties, which gives it the ability to recruit cells of adaptive immunity. Defensins are themselves divided into two families, α and β, based on their secondary structure. The α-defensins (6 known to date) are mainly located in the storage granules of specialized cells such as neutrophils, or intestinal Paneth cells, while β-defensins are characteristic of epithelial tissues. In addition to their role in innate immunity, defensins are also known for their mitogenic properties, which suggests their potential involvement in the healing process. In humans, 4 β-defensins have been identified to date (there are more than 20 genes coding for anti-microbial peptides in our genome). Human β-defensin 1 (hBD-1) is generally produced in a constitutive manner and is expressed in large quantities in the kidneys and to a lesser extent in the pancreas, salivary glands, epithelia of the respiratory tract, in the uro system -general of women, in the healthy synovial membrane, as well as in the placenta. hBD-1 is also expressed in the skin. The other forms of β-defensins, hBD-2, 3 and 4, are inducible. hBD-3 is induced in the inflammatory synovial membranes, for example in arthritis pathologies. Expression of hBD-2 has been reported to date in the skin, urogenital tract, sweat glands, and in the pilosebaceous unit. In the skin, other peptides or proteins, such as adrenomedullin, cystatin, the specific elastase inhibitor / SKALP / elafin, have anti-microbial activities. More recently, dermicidin (broad spectrum of activity) has been characterized as an anti-microbial peptide specific for the skin which is produced in the eccrine sweat glands, and whose simultaneous secretion with sweat would constitute an important part of the system of innate defense against local and systemic infections. hBD-2 was first characterized in psoriasis scales. The expression of hBD-2 and -3, as well as LL-37, is increased in the lesions of psoriasis, which would explain the greater resistance to infections of patients suffering from this pathology. Conversely, in atopic dermatitis (chronic lesions and pushing lesions), the expression of LL-37 and hBD-2 is reduced under the influence of interleukin-4 (IL-4) and l 'interleukin-l 3 (IL-13), mediators of atopy. This deficiency could explain the increased susceptibility to infections of patients with atopic dermatitis. In acne, the expression of β-defensins (hBD-1 and -2) is increased in response to the proliferation of P acnes. In addition, it is assumed that acne sufferers of an initial imbalance in antimicrobial peptides, responsible for bacterial proliferation, bacteria which in turn stimulate the innate immune defenses. Inflammation therefore seems to be a predominant factor in the induction of anti-microbial peptides. Thus, it has also been shown that interleukin-1, TNF-α (Tumor Necrosis alpha), and ultraviolet irradiation stimulate the production of hBD-2. The expression of hBD-2 is also linked to the differentiation state of keratinocytes. Thus, stimulation of the production of antimicrobial peptides, in particular of the defensin family, and more particularly of hBD-2, would make it possible to promote and / or restore innate immunity, in particular in the eyes and in the epithelia ( epidermis, vaginal, intestinal, nasal and auricular mucous membranes, respiratory tract). The oral cavity is constantly exposed to a wide variety of microbes (bacteria, viruses, fungi). Among other things, it is well established that bacteria such as actinobacillus actinomycetemcomitans, porphyromonas gingivalis are key factors participating in the development of periodontal diseases (gingivitis and periodontitis). The gingival epithelium constitutes the first bulwark against the various pathogens present in the oral sphere. As such, the gingival keratinocytes produce a large panel of anti-microbial peptides, hBD-1, -2, -3, LL37. These peptides are also produced in the oral mucosa, as well as by the salivary glands. More particularly, stimulation of anti-microbial peptides would promote and / or restore innate immunity in healthy or pathological skin of infants and children, whose immunity is generally deficient, and in the skin healthy or sick adults or the elderly (immunosuppressed). This stimulation would thus advantageously complement the passive defense system of the skin which constitutes the stratum corneum (corneocytes + intercellular cement), and prepare the adaptive immune response in infants, children, adults and the elderly, in good condition. health or sick. At the same time, this stimulation would promote healing. D-mannoheptulose, the first ketoheptosis identified in 1916 by La Forge, of general formula (I)

is found in certain plants, in particular in alfalfa (Medicago sativa L.), in avocado, in fig (Ficus officinalis L.) and in the primrose (Primula officinalis Jacq.). However, it is in avocado that we find the most important in D-mannoheptulose. D-mannoheptulose has already been used in therapeutic applications. For example, patent application WO95 / 03809 describes the use of D-mannoheptulose, as a glucokinase inhibitor, to inhibit the development of tumor cells and application US2003 / 0092669 describes an oral food supplement comprising D-mannoheptulose , which reduces the insulin level and thus allows weight loss. Perseitol, polyol form of D-mannoheptulose, of general formula (II)

is also found in avocado, especially in the fruit or in the avocado pit. According to the publication "Search for pharmacochemical leads from tropical rainforest plants", Hitotaka Shibuya et al. Pure Appl. Chem., Vol. 71, n ° 6, pp 1 109- 1 1 13, 1999, perseitol, associated with a potassium ion, makes it possible to inhibit the incorporation of leucine- ³ H in tumor cells of Ehrlich sarcomatous ascites.

Surprisingly, the inventors have discovered that a composition comprising D-mannoheptulose and / or perseitol allows the increase in the production of antimicrobial peptides, advantageously hBD-2, without inducing inflammatory reactions, irritations or intolerances in particular without significantly stimulating the secretion of molecules usually expressed in the case of inflammatory reactions. Thus, the subject of the present invention is the use of a composition comprising D-mannoheptulose and / or perseitol and a suitable pharmaceutically acceptable excipient, for the manufacture of a medicament or a veterinary composition intended for the treatment and / or prevention of diseases related to a modification of innate and / or acquired immunity by increasing the production of antimicrobial peptides, of the family of cathelicidines and / or beta-defensins, advantageously hBD-2. Within the meaning of the present invention, the term “modification” can mean increase or decrease. The present invention also relates to the use of a composition comprising D-mannoheptulose and / or perseitol and a suitable pharmaceutically acceptable excipient, for the manufacture of a medicament or a veterinary composition intended for the treatment and / or the prevention of diseases linked to a modification of innate and / or acquired immunity by stimulation of antimicrobial like peptides, such as a specific elastase inhibitor, particularly elfin (SKALP). The medicament or the veterinary composition according to the invention advantageously makes it possible to stimulate and / or supplement innate immunity and / or acquired immunity. In general, in the context of the present invention, said diseases can be linked to the presence of microorganisms, in particular Gram + and / or Gram- bacteria, fungi, yeasts or viruses. More particularly, said diseases can be infections of the ocular and auditory systems, non-keratinized epithelia (vaginal, intestinal, gingival, nasal, pulmonary mucosa, respiratory, anal and urethral, pulmonary) and keratinized epithelia such as the skin. Said diseases can also be infections of the appendages or cutaneous appendages (hair, nails, sweat glands, sebaceous glands). Thus said diseases can be pathologies such as folliculitis, boils, abscesses, impetigo or parsnip. Said diseases can be pathologies of the scalp such as dandruff, and more generally conditions linked to hyper-seborrhea. Said diseases can be pathologies linked to a modification of the Thl / Th2 balance such as atopic dermatitis. Said diseases can be pathologies associated with a modification of the synthesis of cytokines, such as IL-4 and / or PIL-13, in particular in the context of atopic dermatitis. Said diseases can also be inflammatory dermatoses, such as atopic dermatitis, atopic and / or contact eczema, psoriasis, acne, and irritant dermatitis. Said diseases can also be burns, in particular first or second degree burns. Said diseases can also be pathologies linked to a deficit in the skin barrier. Thus, the medicament according to the invention can be used for the treatment of hyper-reactive (sensitive, irritated, allergic), atopic, dry or aged skin. Said diseases can also be pathologies linked to skin weakened by environmental aggression, in particular due to cold, pollution, stress, tobacco, sun exposure. In the context of the present invention, the medicament is also suitable for the protection of immature, healthy or pathological skin, infants and children. Indeed, it strengthens the natural defenses of the epidermis of children whose immunity is generally deficient. In the context of the present invention, the medicament is also suitable for the protection of healthy or pathological skin of adults or of the elderly, in particular of immuno-depressed individuals. The medicament according to the invention is also suitable for promoting healing, in normal or pathological healing processes, such as ulcers and bedsores. In the context of the present invention, the medicament is also intended to treat and / or prevent periodontal diseases, inflammatory joint pathologies such as osteoarthritis, infections of the mucous membranes, in particular of the vaginal, intestinal, respiratory, nasal or atrial mucous membranes , or infections of the eye system. The composition according to the invention advantageously comprises 0.001 to 30% by dry weight of D-mannoheptulose, relative to the total weight of said composition, even more advantageously 0.01-20% by dry weight, even more advantageously 0.1-10 % by dry weight, even more advantageously 0.5-5% by dry weight of D-mannoheptulose. The composition according to the invention advantageously comprises 0.001 to 30% by dry weight of perseitol, relative to the total weight of said composition, even more advantageously 0.01-20% by dry weight, even more advantageously 0.1-10% by weight. dry weight, even more advantageously 0.5-5% by dry weight of perseitol. In the context of the present invention, the terms “D-mannoheptulose” and “perseitol” also cover their chemical derivatives. The source of D-mannoheptulose and / or perseitol can be a water-soluble extract of avocado or other plant sugars. Otherwise, D-mannoheptulose and perseitol are commercially available (synthetic origin). According to an advantageous variant of the invention, the source of D-mannoheptulose and / or perseitol is a water-soluble extract of avocado sugars. The water-soluble extract of avocado sugars can be directly obtained from any part of the avocado or avocado tree, such as the fruit, the skin, the stone, the leaf or the roots of the avocado. It is also possible to obtain an avocado peptide extract from the by-products of the avocado processing industry, among which the following may be mentioned in a non-exhaustive manner: fresh avocado pulp, frozen pulp , dehydrated, avocado cake from the oil extraction process (mechanical and / or solvent extraction of the previously dehydrated fruit), deoiled solid matter from the wet oil extraction process (so-called centrifugation), deoiled solid materials from the processes of extracting avocado oil by enzymatic route, raw avocado purees (guacamole), solid waste from the production units of these purees. The extract is advantageously obtained from fresh avocado fruit. The fruits can be chosen from the Hass, Fuerte, Ettinger, Bacon, Nabal, Anaheim, Lula, Reed varieties,

Zutano, Queen, Criola Selva, Mexicana Canta, Dschang Region, Hall, Booth, Peterson,

Collinson Redn, more advantageously the Hass, Fuerte and Reed varieties. Preferably, we will use the Hass, Fuerte, Ettinger and Bacon varieties, and more advantageously the Hass and Fuerte varieties. The avocado fruit consists mainly of water, pulp, oil and stone. The proportions of these constituents are, like all natural and vegetable materials, extremely variable. However, the following average composition data are generally accepted, expressed as a percentage of fresh fruit, given in table 1 below: Table 1 In fact, avocado is not particularly rich in polysaccharides. However, the nature of the soluble monosaccharides is quite particular, such as perseitol or D-mannoheptulose consisting of 7 carbon atoms. The water-soluble extract of avocado sugars can be obtained by a process comprising the following successive stages: - obtaining an avocado cake, advantageously from the avocado fruit, by drying the avocado and then extracting lipids (oil); then - cryogenic grinding and complete delipidation of said cake, then decantation and centrifugation in order to recover a soluble fraction rich in C7 sugars (elimination of the cake); - demineralization on ionic resin of said soluble fraction, obtained in the previous step; then - ultrafiltration at 10,000 daltons; and - where appropriate, vacuum concentration and packaging. The first step in the process is to dry the fruit and then to oil it. Thus, after slicing the fruit into thin strips, it can be dried using all of the techniques known to those skilled in the art, among which mention may be made of drying with hot air, lyophilization or even osmotic drying. In general, the temperature during this drying step will advantageously be maintained, whatever the technique used, less than or equal to 80 ° C. In the context of the present process, for reasons of ease of implementation and for reasons of cost, drying in ventilated dryers, in a thin layer and under a stream of hot air, at a temperature of between 70 and 75 ° C. is preferred. The duration of the operation can vary from 5 to 72 hours. The lipids of the dried fruit are subsequently extracted either mechanically in a continuous screw press, or alternatively chemically, using a solvent such as hexane, in a soxhlet type extractor or in a continuous belt extractor, of the De Smet® type, in particular according to the method described in application FR 2 843 027, or by a process using supercritical CO ₂ . Among the major interests of the process, the co-produced oil constitutes a product which is obviously directly recoverable. This is why, the extraction of lipids by mechanical means is preferred. The dry and de-oiled fruit, or also called oil cake, can then undergo the following stages: complete cryogenic grinding, especially with acetone and / or ethanol, - decantation then washing of the oil cake with water, centrifugation, recovery of the soluble fraction (elimination of the cake), demineralization by ion exchange ultrafiltration with a cutoff threshold of 10 kD concentration in vacuum, addition of preservative and packaging. In general, the final aqueous extract may contain by weight 0.1 to 10% of dry matter, advantageously 1 to 7% of dry matter, even more advantageously 3 to 5% of dry matter. The content of sugars in C7, that is to say in D-mannoheptulose and in perseitol, in the dry matter is advantageously comprised in 65 to 90% by weight, relative to the total weight of the dry matter. The average analytical data of a 5% aqueous solution of dry extract, obtained by the process described above, are given in Table 2 below:

The relative sugar composition of the water-soluble extract, by weight relative to the total weight of the dry matter of the extract, advantageously meets the following criteria (relative composition determined by HPLC; high performance liquid chromatography = high performance liquid chromatography): - D-mannoheptulose 5 to 80% - Perseitol 5 to 80% - Sucrose less than 10% - Glucose less than 10% - Fructose less than 10% The water-soluble extract of avocado sugar advantageously comprises, relative to the total weight of the dry matter, 10 to 80% by weight of D-mannoheptulose more advantageously 15 to 70% by weight of D-mannoheptulose. The water-soluble extract of avocado sugar advantageously comprises, relative to the total weight of the dry matter, 20 to 80% by weight of perseitol, more advantageously 25 to 70% by weight of perseitol. Preferably, the relative sugar composition of the water-soluble extract, by weight relative to the total weight of the dry matter of the extract, meets the following criteria (relative composition determined by HPLC): - D-mannoheptulose 25 at 60% > - Perseitol 25 to 60% - Sucrose less than 10%> - Glucose less than 10% - Fructose less than 10% Surprisingly, the inventors have found a synergistic effect between D-mannoheptulose and / or perseitol and minority sugars (fructose, glucose, sucrose) present in the extract of avocado sugars. The extract obtained may optionally be lyophilized in order to obtain a solid powder (dry extract), completely water-soluble. According to an advantageous variant of the invention, the composition also comprises an avocado peptide extract, advantageously in a proportion of 0.001 to 30%> by dry weight, even more advantageously 0.01 to 20% by dry weight, even more advantageously 0.1 to 15% by dry weight, even more advantageously 0.5 to 10% by dry weight, even more advantageously 0.7 to 8%> by dry weight, and even more advantageously 1 to 5% by dry weight, relative to the total weight of the composition. A synergistic effect is then advantageously observed. The avocado peptide extract, added to the composition according to the invention, advantageously comprises 2 to 10%> by weight of alpha-amino nitrogen, relative to the weight of the dry matter of the peptide extract. In the context of the present invention, the term "alpha-amino nitrogen" means the nitrogen content of the peptides under the form of free alpha-amino groups. The measurement of the alpha-amino nitrogen content of the peptides makes it possible to evaluate the degree of hydrolysis of the proteins as well as the average molar mass of the peptides. More particularly, the avocado peptide extract can be obtained by a process comprising the following steps: - obtaining an avocado cake, advantageously from the avocado fruit, by drying the avocado and then extracting lipids; then - cryogenic grinding and complete delipidation of said cake then decantation, centrifugation and recovery of the cake; then - first hydrolysis in the presence of glucanases, followed by centrifugation and elimination of the soluble fraction; - second hydrolysis in the presence of one or more proteases, followed by centrifugation and elimination of the pellet; then - concentration of the peptide phase by nanofiltration; - discoloration, in the presence of activated carbon for example, followed by simple filtration (10 μm) then by ultrafiltration (cutoff threshold of 10 kD); finally - if necessary, final sterilizing microfiltration (0.2 μm), addition of preservative and packaging. The obtaining of the avocado cake and the extraction of the lipids are advantageously carried out in an identical manner for the peptide extract of avocado and the avocado sugars. The dry and de-oiled fruit, or also called oil cake can then undergo the following stages: complete cryopreservation delipidation, in particular with ethanol and / or acetone, - decantation, then washing of the oil cake with water, centrifugation, recovery of the cake, - first hydrolysis in the presence of one or more glucanases, centrifugation, elimination of the soluble fraction, second hydrolysis in the presence of one or more proteases, - centrifugation, elimination of the pellet, concentration by nanofiltration - discoloration, in particular in the presence of charcoal, - simple filtration (10 μm) then ultrafiltration (cutoff threshold of 10 kD), packaging and addition of preservative, - final sterilizing microfiltration (0.2 μm) addition of preservative and packaging. The final aqueous extract may contain by weight 1 to 60% of dry matter, or even 3 to 20% of dry matter, preferably 5 to 6% of dry matter. The extract obtained may optionally be lyophilized in order to obtain a solid powder (dry extract), but completely water-soluble compared to the original proteins of avocado. Relative to the weight of the dry matter, the content of alpha amino nitrogen may be between 2 and 10%> by weight, preferably between 5 and 7% by weight. The pH of an aqueous solution at 1.2%> by weight of dry extract, relative to the weight of the dry matter, will generally be between 3 and 6, more advantageously between 4 and 5. According to an advantageous variant of l invention, the composition also comprises a lupine peptide extract, advantageously in a mass amount, relative to the total weight of the composition, from 0.001 to 30%> by dry weight, even more advantageously from 0.01 to 10% dry weight. The lupine peptide extract, added to the composition according to the invention, comprises at least 70%>, advantageously at least 80% o, by weight of peptides, relative to the weight of the dry matter of the peptide extract. A synergistic effect is then advantageously observed. In particular, the lupine peptide extract can be obtained by a process comprising the following steps: - preparation of a ground lupine cake or a micronized lupine flour; - then delipidation by extraction with a solvent - extraction of soluble protein and sugar fractions, or precipitation of proteins at the isoelectric point; - optionally separation of the protein fraction; - enzymatic hydrolysis of the protein fraction, and recovery, possibly after filtration, of the peptide extract. The process for preparing a peptide extract is described in patent application FR 2 792 202, filed by the Expanscience laboratories. The composition may also comprise at least one compound chosen from the group consisting of emollients, moisturizing active agents, activators of synthesis keratin, keratoregulators, keratolytics, skin barrier restructuring agents (activators of skin lipid synthesis, PPARs or Peroxysome Proliferator Activated Receptor agonists), activators of keratinocyte differentiation (retinoids, calcidone®, calcium) , antibiotics, anti-bacterial agents, antifungal compounds, anti-viral agents, sebo-regulators, such as 5-alpha reductase inhibitors, in particular the 5-alpha Avocuta® active agent sold by Laboratoires Expanscience, immunomodulators, such as tacrolimus, pimecrolimus, oxazolines, preservatives, anti-irritant agents, soothing agents, filters and sunscreens, anti-oxidant agents, growth factors, healing agents or molecules eutrophics, anti-inflammatory drugs and agents, and compounds containing unsaponifiables from vegetable oils. Activators of the synthesis of keratin which can be used within the framework of the present invention in association with D-mannoheptulose and / or perseitol are advantageously retinoids, lupine peptides (marketed by the company Silab), key proteins of the stratum corneum or granulosum (keratins). The antibiotics which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously fucidic acid, penicillin, tetracyclines, pristinamycin, erythromycin, clindamycin, mupirocin, minocycline, doxycycline. The anti-viral agents which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously acyclovir and valacyclovir. The anti-irritant agents which can be used within the framework of the present invention in association with D-mannoheptulose and / or perseitol are advantageously glycine, sugars and / or peptides of lupine, Cyclocéramide® (derivative of oxazoline). The soothing agents which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously alpha bisabolol, the liquorice derivatives. The keratorregulators which can be used within the framework of the present invention in association with D-mannoheptulose and / or perseitol are advantageously alpha hydroxy acids and their derivatives. A keratolytic which can be used within the framework of the present invention in association with D-mannoheptulose and / or perseitol is in particular salicylic acid and its derivatives. The antioxidants that can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously vitamins (C, E), trace elements (copper, zinc, selenium). The growth factors which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously becaplermine and TGF-beta (Transforming Growth Factor beta). The healing agents which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously vitamin A, panthenol, Avocadoturane®, zinc oxide, magnesium, silicon, l madecassic or asian acid. The drugs which can be used within the framework of the present invention, in combination with D-mannoheptulose and / or perseitol, are advantageously the drugs, suitable for administration for topical or oral route, for prevention and / or treatment of atopy (corticosteroids, emollients), acne (antibiotics, benzoyl peroxide, retinoids, azelaic acid, vitamin PP, zinc, cyclins), eczema (immunomodulators, emollients, salmon oil, borage, pre -biotics) or psoriasis (corticosteroids, calcipotriol, calcitriol, tazarotene, cade oil, acitretin, PUVA therapy). The anti-inflammatory agents which can be used in the context of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously steroidal anti-inflammatory agents (AIS), such as corticoids, or non-steroidal (NSAIDs) . Agents which restructure the skin barrier, making it possible to stimulate the synthesis of key lipids of the epidermis, and which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously sunflower concentrates, even more advantageously linoleic sunflower concentrates, such as the active agent sold by Laboratoires Expanscience, Soline® (cf. international application WO 01/21150), unsaponifiables of vegetable oil, such that Avocadoturane® (cf. international application WO 01/21 150), PPAR agonists (rosiglitazone, pioglitazone). The restructuring agents are advantageously present in a proportion ranging from 0.001 to 30% by weight, relative to the total weight of the composition or of the medicament. Antifungal compounds that can be used in the scope of the present invention in combination with D-mannoheptulose and / or perseitol are advantageously econazole and ketoconazole. The antiseptic preservatives which can be used within the framework of the present invention in association with D-mannoheptulose and / or perseitol are for example triclosan, chlorhexidine, quaternary ammoniums. The immunododulators which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously tacrolimus, pimecrolimus and oxazolines. The oxazolines which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously oxazolines chosen from the group consisting of 2-undecyl-4-hydroxymethyl- 4-methyl-1,3-oxazoline, 2-undecyl-4,4-dimethyl-1,3-oxazoline, (E) -4,4-dimethyl-2-heptadec-8-enyl-1,3, oxazoline, 4-hydroxymethyl-4-methyl-2-heptadecyl-1, 3-oxazoline, (E) -4-hydroxymethyl-4-methyl-2-heptadec-8-enyl-1,3-oxazoline, 2 -undecyl-4-ethyl-4-hydroxymethyl-1,3-oxazoline. Even more advantageously, said oxazoline is 2-undecyl-4,4-dimethyl-1,3-oxazoline, called OX-100 or Cycloceramide®. The compounds containing unsaponifiables of vegetable oils which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously chosen from the group consisting of furan lipids d avocado, avocado and soy unsaponifiables, lupine oil concentrates, sunflower oil concentrates and mixtures thereof. The avocado furan lipids which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously natural 2-alkyl furans, in particular the active ingredient Avocadofurane® marketed by Laboratoires Expanscience, which can be obtained by the process described in international application WO 01/21605. The unsaponifiables of avocado and soya which can be used within the framework of the present invention in association, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously a mixture of unsaponifiables of furan avocado and soy unsaponifiables, in a respective ratio of approximately 1 / 3- 2/3. The unsaponifiables of avocado and soy are even more advantageously the product Piasclédine®, marketed by Laboratoires Expanscience. The lupine oil concentrates which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and or perseitol are advantageously concentrates obtained by molecular distillation of lupine oil, advantageously sweet white lupine oil, such as those described in international application WO 98/47479. They advantageously contain approximately 60%> by weight of unsaponifiables. The sunflower oil concentrates which can be used in the context of the present invention in combination, advantageously with a synergistic effect, with D-mannoheptulose and / or perseitol are advantageously linoleic sunflower concentrates, such as the active ingredient marketed by Laboratoires Expanscience, Soline® (cf. international application WO 01/21150). The composition according to the invention can be formulated in the form of various preparations suitable for topical administration, for oral, rectal, vaginal, nasal, auricular or bronchial administration, for parenteral administration. Preferably the different preparations are suitable for topical administration and include creams, ointments, lotions, oils, patches, sprays or any other product for external application. The optimal modes of administration, the dosages and the galenical forms of the compounds and compositions according to the invention can be determined according to the criteria generally taken into account in the establishment of a pharmaceutical treatment, in particular dermatological, or veterinary adapted to a patient or an animal such as for example the age or body weight of the patient or the animal, the seriousness of his general condition, the tolerance to the treatment, the side effects observed, the type of skin. Depending on the type of administration desired, the composition and or the active compounds according to the invention may also comprise at least one pharmaceutically acceptable excipient, in particular dermatologically acceptable. Preferably, an excipient suitable for administration by external topical route is used. The composition according to the present invention can also comprise at least one adjuvant pharmaceutically known to those skilled in the art, chosen from thickeners, preservatives, perfumes, dyes, chemical or mineral filters, moisturizers, thermal waters, etc. The present invention also relates to a medicament or a veterinary composition comprising 0.001 to 30%> by weight of D-mannoheptulose and 0.001 to 30% by weight of perseitol, relative to the total weight of said medicament, even more advantageously 0.0 to 10% > by weight of D-mannoheptulose and 0.01 to 10%> by weight of perseitol, and a suitable pharmaceutically acceptable excipient. The medicament or the veterinary composition according to the invention can be formulated under the form of different preparations suitable for topical administration, for oral or rectal, vaginal, urethral, auricular, bronchial, nasal administration, for parenteral administration. The optimal modes of administration, the dosages and the galenical forms of the drug or of the veterinary composition according to the invention can be determined according to the criteria generally taken into account in the establishment of a pharmaceutical treatment, in particular dermatological, adapted to a patient, or veterinarian. The present invention also relates to a cosmetic composition comprising 0.001 to 30% by weight of perseitol and 0.001 to 30%> by weight of D-mannoheptulose, relative to the total weight of said composition, even more advantageously 0.01 to 10%> weight of perseitol and 0.01 to 10% o by weight of D-mannoheptulose. According to an advantageous variant of the invention, the source of D-mannoheptulose and / or perseitol is a water-soluble extract of avocado sugars, which can be obtained by a process as described above. There is indeed a synergy between D-manoheptulose, perseitol and the minority sugars of avocado

(fructose, glucose, sucrose). According to an advantageous variant of the invention, the composition also comprises an avocado peptide extract, advantageously in a synergistic amount.

The avocado peptide extract is advantageously present in an amount of 0.001 to 30

% _> , more advantageously from 0.1 to 10%>, by dry weight, relative to the total weight of the composition. The avocado peptide extract, added to the composition according to the invention, advantageously comprises 2 to 10% by weight of alpha-amino nitrogen, relative to the weight of the dry matter of the peptide extract. It can be obtained according to a process as described above. According to an advantageous variant of the invention, the composition also comprises a lupine peptide extract, advantageously in a synergistic amount. The lupine peptide extract is advantageously present in an amount of 0.001 to 30%>, more advantageously 0.1 to 10%, by dry weight, relative to the total weight of the composition. The lupine peptide extract, added to the composition according to the invention, comprises at least 70%, advantageously at least 80%>, by weight of peptides, relative to the weight of the dry matter of the peptide extract. It can be obtained according to a process as described above. The composition may also comprise at least one compound chosen from the group consisting of restructuring agents of the skin barrier and the compounds containing unsaponifiables from vegetable oils, as defined above advantageously in a synergistic amount. In particular, the cosmetic composition may comprise an active agent chosen from the group consisting of Soline®, Avocadofurane® and piasclédine®, marketed by Laboratoires Expanscience. The cosmetic composition according to the invention advantageously comprises 0.001 to 30%> by weight, relative to the total weight of the composition, of at least one agent which restructures the skin barrier. The cosmetic composition according to the invention can be formulated in the form of various preparations suitable for topical administration, for oral or rectal, vaginal, urethral, auricular, nasal, bronchial administration. Preferably, the various preparations are suitable for topical administration and include creams, ointments, lotions, oils, patches, sprays or any other product for external application. Depending on the type of administration desired, the composition and / or the active compounds according to the invention may also comprise at least one cosmetically acceptable excipient. The cosmetic composition according to the present invention can also comprise at least one adjuvant cosmetically known to those skilled in the art, chosen from thickeners, preservatives, perfumes, dyes, chemical or mineral filters, hydrating agents, waters spas, etc. The present invention also relates to a cosmetic treatment method for sensitive, irritated, allergic, dry, aged, intolerant skin and / or mucous membranes, having a cutaneous barrier disorder, weakened by aggression. environmental showing redness of the skin or having a non-pathological immunological imbalance, characterized in that it consists in applying to the skin and / or the mucous membranes a cosmetic composition according to the invention. The present invention finally relates to a nutraceutical composition comprising D-mannoheptulose and / or perseitol and a suitable acceptable food excipient. The nutraceutical composition according to the invention advantageously comprises 0.001 to 30% by weight of D-mannoheptulose, relative to the total weight of said composition, even more advantageously 0.01 to 10% by weight of D-mannoheptulose. The nutraceutical composition according to the invention advantageously comprises 0.001 to 30% by weight of perseitol, relative to the total weight of said composition, even more advantageously 0.01 to 10%> by weight of perseitol. The nutraceutical composition according to the invention advantageously comprises 0.001 to 30%> by weight of perseitol and 0.001 to 30% o by weight of D-mannoheptulose, relative to the total weight of said composition, even more advantageously 0.01 to 10% in weight of perseitol and 0.01 to 10%> by weight of D-mannoheptulose. According to an advantageous variant of the invention, the source of D-mannoheptulose and / or perseitol is a water-soluble extract of avocado sugars, which can be obtained according to a process as described above. According to an advantageous variant of the invention, the composition also comprises an avocado peptide extract, advantageously in a synergistic amount, advantageously in an amount of 0.001 to 30%> by dry weight, relative to the total weight of the composition. The avocado peptide extract, added to the composition according to the invention, advantageously comprises 2 to 10%> by weight of alpha-amino nitrogen, relative to the weight of the dry matter of the peptide extract. It can be obtained according to a process as described above. According to an advantageous variant of the invention, the composition further comprises a lupine peptide extract, advantageously in a synergistic amount, advantageously in an amount of 0.001 to 30%> by dry weight, relative to the total weight of the composition. The lupine peptide extract, added to the composition according to the invention, comprises at least 70%>, advantageously at least 80%, by weight of peptides, relative to the weight of the dry matter of the peptide extract. It can be obtained according to a process as described above. The following examples illustrate the present invention, they are not limiting.

Example 1: preparation of a water-soluble extract of avocado sugars 50 kg of fresh avocados, of the Hass variety, are cut into thin strips 2 to 5 mm thick, including the core, using a disc slicer. The drying tool is a thermo-regulated oven with a current of hot air. The sliced avocados are spread over a thickness of 4 to 5 cm on stepped shelves. The drying temperature is set at 80 ° C, its duration is 48 hours. Once dried, the fruits are subjected to cold pressing. This operation is carried out on a small Komet® laboratory press. The 4 kg of delipidated fruit (oil cake) are then cold ground and then extracted under reflux, in the presence of 25 liters of ethanol. The powder exhausted in lipids is then recovered by filtration on Bϋchner and dried in an oven at 50 ° C for 5 hours. The cake is then washed with demineralized water (10 liters) and then separated by centrifugation. The soluble (liquid) fraction is taken up to be purified and concentrated according to the following procedure:

• Demineralization using ion exchange resins: demineralization of heptuloses by passage over OH ^" resins, then over H ⁺ resin. • Ultrafiltration over 10,000 Da: ultrafiltration is carried out with a system equipped with 4 threshold membranes cutoff 10 kDa.

• Concentration under vacuum: the concentration of the purified extract is carried out using a vacuum evaporator until a dry matter close to 4% is obtained.

• Conditioning: the concentration of the extract is adjusted to 5% of dry matter and preservative is added, then it is sterile filtered with a membrane of 0.2 μm cut-off threshold and it is conditioned. Table 3 below gives the composition of the C7 avocado sugar extract, at 5% dry matter, prepared according to the process described above: Table 3 Following this same process, two other extracts were prepared, the pH value, the absorbance and the sugar content of C7 are given in Table 4 below. The C7 sugar content corresponds to the sum of perseitol and D-mannoheptulose analyzed by HPLC.

Table 4 Example 2: preparation of an avocado peptide extract 50 kg of fresh avocados, of the Hass variety, are cut into thin strips 2 to 5 mm thick, including the nucleus, using a disc slicer. The drying tool is a thermo-regulated oven with a current of hot air. The sliced avocados are spread over a thickness of 4 to 5 cm on stepped shelves. The drying temperature is set at 80 ° C, its duration is 48 hours. Once dried, the fruits are subjected to cold pressing. This operation is carried out on a small Komet® press laboratory. The 4 kg of delipidated fruit (oil cake) are then cold ground and then extracted under reflux, in the presence of 25 liters of ethanol. The powder exhausted in lipids is then recovered by filtration on Buchner and dried in an oven at 50 ° C for 5 hours. The cake is then washed with demineralized water (10 liters) and then separated by centrifugation. The solid fraction is taken up in an aqueous solution, acidified with HCl (pH fixed at 5), then placed in the presence of 2% of cellulases relative to the dry matter. The hydrolysis time is fixed at 6 hours. The mixture is then centrifuged at 2000 g in the presence of adjuvant (2.5% w / v). The recovered pellet then undergoes a second hydrolysis at pH 8.0, in the presence of 0.5% of Alcalase® (commercial enzyme of the protease class), at a temperature of 55 ° C, for 2 hours. The hydrolysis is regulated at constant pH by continuous addition of 2M sodium hydroxide. The protease is finally denatured by heating for 10 minutes, at 85 ° C. The mixture obtained is centrifuged and the supernatant filtered by passage through a 7.5 μm membrane. It is then ultrafiltered on membranes having a cutoff threshold of 10 kD. The crude peptide extract obtained at 20% dry matter, is discolored in the presence of 1% Norit® activated carbon, then filtered again through a 7.5 μm membrane. The discolored extract is then micro filtered (0.2 μm), adjusted in title to the level of 5%> of dry matter, then supplemented with a preservative (0.4% w / v of Phenonip®) and finally conditioned. The characteristics of the peptide extract of water-soluble avocado at 5% dry matter, obtained by this process are given in Table 5 below:

Table 5 According to this same process, other extracts were prepared, the analytical data of which are given in Table 6 below.

Table 6 ¹ N x 6.25 corresponds to the determination of total nitrogen (N) of a sample multiplied by a specific coefficient for the protein assayed. When the coefficient of the proteins measured is not precisely known, the coefficient 6.25 is used by convention. In the aminogram given in Table 7 below, the values are expressed as a percentage by weight relative to the total weight of the amino acids dosed. The values for aspartic acid and glutamic acid also include the contents of asparagine and glutamine, respectively.

Unmeasured tryptophan Table 7 In Examples 3 to 7, unless otherwise indicated, the percentages are expressed by weight relative to the total weight of the dry matter. Example 3 Induction of Beta Defensin-2 by avocado sugars I. Cell seeding (D0): Normal human keratinocytes are seeded in a 96-well plate (approximately 20,000 cells / well), in the presence of a medium specific enriched in calcium (final concentration 1.3 mM), as previously described in the publication "Human-Defensin-2 production in Keratinocytes is regulated by Interleukin-1, Bacteria, and the State of Differentiation", Alice Y. Liu and al., The Society for Investigative Dermatology, vol. 118, No. 2, Feb. 2002, pages 275 to 281. II. Cell treatment (Jl): After a 24-hour incubation at 37 ° C, 5%. CO ₂ : • => 2 rinses with 200 μl / well of PBS (phosphate buffer in saline solution) "=> stimulation of the cells with 200 μl / well (in medium supplemented with Ca ^" "^" ): * with the water-soluble extract avocado sugars at concentrations of 0.5, 0.05 and 0.005% w / w of dry matter "by Il-lβ at a concentration of 100 ng / ml (positive control of hBD-2 induction) III. End of treatment (32): ELISA After 24 hours of incubation, the induction of hBD-2 is evaluated by a technique

ELISA with a specific antibody (goat polyclonal to human BD2; Abcam; ab9871). The results obtained with the water-soluble extract of avocado sugar, batch A, containing 40% "of D-mannoheptulose and 40%> of perseitol, relative to the dry matter, are summarized in Table 8 below: Table 8 * Statistically significant compared to control cells (p <0.05 Student Test) MTT: Methyl Thiazolyl Tetrazolium It is observed that, the water-soluble extract of avocado sugars, batch A, according to the invention makes it possible to increase the amount of hBD-2 produced. The results obtained with batch B, containing 10%> of D-mannoheptulose and 70% of perseitol, relative to the dry matter, are summarized in Table 9 below: OD = optical density

Table 9

* Statistically significant compared to control cells (p <0.05 Student Test) It is observed that, in a dose-dependent manner, the soluble extract of sugars avocado, lot B, increases hBD-2 production.

Example 4: Effect of avocado sugars on the expression of hBD-2 in epithelial cells. 1. Cells KB cells (ATCC CCL-17), a line of epithelial cells from a human oral carcinoma, commonly used in studies on the oral cavity, were seeded in 96-well plates and cultured in RPMI 1640 (Roswell Park Memorial Institute Medium) with 10% Glutamax ™ I> SVF (fetal calf serum) + antibiotics. 2. Treatment After 24 hours of incubation, the culture medium was eliminated and the cell carpet was rinsed twice with PBS. The cells were then treated under the conditions defined below for 24 and 48 hours: ^• Control cells: medium alone -> TNFα (marketed by Sigma) at 100 ng / ml - ^ water-soluble extract of avocado sugars (40% mannoheptulose / 40% perseitol) at 0.005-0.05 and 0.5% w / w (dry matter) (lot A) 3. End of treatment ^ Determination of anti-microbial peptides by ELISA on cells After 48 hours of incubation under the different treatment conditions, the β-defensins 2 and 3 as well as LL-37 present in the KB cells were assayed by an ELISA technique on cells. To determine the number of total cells in each well, a

MTT was carried out in parallel on cells treated under the same conditions. ^ Exploitation of the results For each treatment condition, the OD ₄₅ o PAMs (Antimicrobial peptides) was divided by the OD ₅ - ₇₀ MTT to obtain the quantity of PAMs produced per living cell. The means and standard deviations were calculated for each condition and the induction of the different PAMs was calculated as the percentage increase compared to the control cells. 4. Results Induction of HBD-2 The TNF-α used here as a positive control of the induction of PAMs leads to a significant increase in the production of hBD-2 by KB cells by 239% "at 48 hours. This test validates the model. The water-soluble extract of avocado sugars also induces a statistically significant increase in the production of hBD-2 in KB cells (see results in Table 10).

Table 10 Induction of HBD-3 The TNF-α used here as a positive control of the induction of PAMs causes a significant increase in the production of hBD-3 by KB cells by 30% at 48 h. This test validates the model. The water-soluble extract of avocado sugars also induces a statistically significant increase in the production of hBD-3 in KB cells (see results in Table 11). Table 11 Induction of LL-37 The TNF-α used here as a positive control of the induction of PAMs causes a significant increase in the production of LL-37 by KB cells by 88%> at 48 h. This test validates the model. The water-soluble extract of avocado sugars also induces a statistically significant increase in the production of LL-37 in KB cells. (see results in table 12)

Table 12 In conclusion, it has been demonstrated that avocado sugars (water-soluble extract of avocado sugars) are capable of inducing the synthesis of antimicrobial peptides, and in particular hBD-2, -3 and LL-37 in KB type epithelial cells. Example 5: Effect of avocado sugars on pro-inflammatory molecules Procedure: Normal human keratinocytes are seeded in a 24-well plate (approximately 50,000 cells / well), in the presence of a specific medium enriched in calcium (final concentration 1.3 M), as previously described in the publication "Human /? - Defensin-2 production in Kératinocytes is regulated by Interleukin-1, Bacteria, and the State of Differentiation", Alice Y. Liu et al., The Society for Investigative Dermatology, vol. 118, No. 2, Feb. 2002, pages 275 to 281. The cells were treated for 24 h in the presence of 0.05%> w / w avocado sugars (batch A, 40%> mannoheptulose / 40%> perseitol). The pro-inflammatory cytokines IL-lβ, IL-8 and TNF-α were assayed by an ELISA technique (R&D System kits) in the culture supernatants. Cell viability is measured by a neutral red test. The results are expressed as a function of the neutral red OD in order to reduce the quantity of cytokines produced to the quantity of living cells (Tables 13, 14, 15). Results:

Table 13

Table 14

Table 15

Conclusion: Avocado sugars (water-soluble extract of avocado sugars) do not induce the production of pro-inflammatory molecules usually co-expressed with beta-defensins (IL-1, IL-8, TNF-α). Thus, avocado sugars are inducers of PAMs without being pro-inflammatory. Example 6: Modulation of the synthesis of HBD-2 by the various sugars present in the extract of avocado sugars The same test as in Example 3 was carried out using: a mixture of fructose (5%> ), glucose (5%) and sucrose (3%); D-mannoheptulose (40%); - perseitol (40%); - a mixture of fructose (5%>), glucose (5%), sucrose (3%) and D-mannoheptulose (40%>); a mixture of fructose (5%>), glucose (5%), sucrose (3%>) and perseitol (40%>); - a mixture of fructose (5%), glucose (5%>), sucrose (3%), D-mannoheptulose (40%>) and perseitol (40%>); and - an extract of avocado sugars (lot A). The extract of avocado sugars comprises 40%> by weight of D-mannoheptulose and 40% by weight of perseitol, relative to the total weight of the dry matter. The results are given in the following table 16:

Table 16 The avocado minority sugars (fructose, glucose and sucrose) have no activity on the synthesis of HBD-2. In an equal amount (40% by weight, relative to the weight of the dry matter), D-mannoheptulose is more active than perseitol. When D-mannoheptulose and or perseitol is mixed with the minority sugars of avocado (fructose, glucose and sucrose), there is a synergistic effect. The mixture of fructose, glucose, sucrose, perseitol and D-mannoheptulose (said reconstituted mixture) and the water-soluble extract of avocado sugars obtained in Example 1 have equivalent activity.

Example 7: Activity of D-mannoheptulose and perseitol of commercial origin. The same test as in Example 3 was carried out using commercially available D-mannoheptulose and perseitol. The results are given in the following table 17: Table 17 D-mannoheptulose and perseitol, tested separately, are capable of inducing the production of hBD-2.

Example 8 Effect of Avocado Sugars on the Expression of HBD-2 Modulated by IL-4 in the In Vitro Modeling of Atopic Dermatitis

Normal human keratinocytes are seeded as described in Example 3. After an incubation of 24 h at 37 ° C, 5% CO ₂ , the culture medium is eliminated and the cell carpet rinsed twice with PBS. The cells are then treated for 24 hours under the conditions defined below: Control cells: medium alone - Il-lβ at 100 ng / ml (positive control of hBD-2 induction) - 11-4 at 50 ng / ml - Water-soluble extract of avocado sugars (batch A) at 0.05% w / w of dry matter - Il- 1 β at 100 ng / ml and 11-4 at 50 ng / ml - 11-4 at 50 ng / ml and water-soluble extract of avocado sugars (lot A) at 0.05%> w / w dry matter Il-lβ at 100 ng / ml and 11-4 at 50 ng / ml and water-soluble extract of sugar avocado (lot A) at 0.05% op / w of dry matter At the end of the treatment, the induction of hBD-2 is evaluated by an ELISA technique on cells, in parallel, the number of total cells present in each well is determined by an MTT test carried out in parallel on treated cells. under the same conditions. Thus for each condition, the OD ₅ o hBD-2 is divided by the OD ₅₇ o MTT to obtain the amount of hBD-2 produced per living cell. The results are presented in Table 18 below:

Table 18 * p <0.01; ** p <0.05 compared to control cells (Student T test) *** ρ <0.05 compared to positive control (Student T test) **** p <0.01 compared to Il -lβ + 11-4 (Student's T test)

The positive control II-1 β induces a significant increase in the synthesis of hBD-2 compared to the control cells (+ 80%>). In the same way, the water-soluble extract of avocado sugars, batch A, causes an increase in the synthesis of bJBD2 (+ 48%>). Il-4 alone has no influence on the amount of hBD-2 expressed by keratinocytes. In the presence of Il-4, the synthesis of hBD-2 induced by Il-lβ is significantly inhibited by 32%. Under these conditions, the addition of lot A to Il-lβ + 11-4 makes it possible to re-increase the synthesis of hBD-2: significant increase of 152%) compared to Il-l β + 11-4. Conclusion: Atopic dermatitis is characterized by a deficiency in antimicrobial peptides (hBD-2, hBD-3, LL-37). This deficiency is explained in particular by a deregulation of the TH1 / TH2 balance and an overproduction of the TH2 cytokines (11-4 and II- 13). In this model, we have shown that the water-soluble extract of avocado sugars is capable of countering the inhibition of hBD2 induced by H-4. Avocado sugars therefore have an interest in the management of atopic dermatitis.

EXAMPLE 9 Cosmetic Formulations According to the Invention Anti Acne Cream No. 1 Isononyl Isononanoate 7,000 Di-C _12- i ₃ Alkyl Malate 7,000 Isocetyl Stearate 5,000 Butylene Glycol 3,000 Oriza Sativa 2,500 Water Soluble Avocado Sugar Extract 3,000 Dicaprylyle Ether 2,000 Salicylate Silanediol 2,000

1.650 peanut alcohol

Tromethamine 1,180

Cetyl alcohol 1,000

Salicylic acid 1,000

Ascorbyle glucoside 1,000

Wisteria 1,000

Tocopheryl acetate 1,000

Behenyl alcohol 0.900

0.790 Squalane

Sodium Citrate 0.660

PPG-12 / SMDI 0.500 copolymer

Glucoside Arachidyle 0.450

Perfume 0.400

0.160 sclerotium gum

Cetearyl alcohol 0.130

Citric acid 0.110

Sepigel 305 * 0.100

QS conservative system

Water QSP 100

^ product marketed by the company Seppic Foaming cleansing emulsion for acne-prone skin no. Water QSP 100 Arlatone duo * 20.00000 Coconut glucoside 12.00000 Hydroxypropyl guar 2.00000 Soluble extract of avocado sugars 1.00000 PEG-200 palmate Glyceryl hydrogenated 1, 10000 PEG-7 Cocoate Glyceryl 1, 10,000 Silanediol Salicylate 1, 00,000 Cocamide DEA 1.00000 Caprylyol Glycine 0.50000 Potassium Sorbate 0.50000

Polyquaternium 10 0.40000

Perfume 0.40000 Citric Acid 0.30000

Zinc PCA 0,20000 ^ product marketed by the company Quimasso Foaming washing emulsion for acneic skin n ° 2

Eau QSP 100 Arlatone duo * 20.00000

Coco-Glucoside 12.00000

Guar Hydroxypropyl 2.000000

Soluble extract of avocado sugars 2.000000

PEG-200 Glyceryl hydrogenated palmitate 1, 10000 PEG-7 Glyceryl cocoate 1, 10000

Silanediol salicylate 1.00000

Cocamide DEA 1.00000

Caprylyol glycine 0.50000

Potassium Sorbate 0.50000 Polyquaternium 10 0.40000

Perfume 0.40000

Citric Acid 0.30000

Zinc PCA 0,20000 ^ product sold by the company Quimasso Toothpaste Water QSP 100 Soluble extract of avocado sugars 2.00 Sodium monofuorophosphate 0.75 Sodium fluoride 0, 10 Sorbitol at 70% 35 Synthetic silica with high abrasive power 13 Synthetic silica with low abrasive power 5

Carboxymethylcellulose sodium 1, 6 Sodium lauryl sulfate 1

Menthol flavor 0.85

Titanium oxide 0.5

0.5 soda lye

Sodium cyclamate 0.3 Menthol 0.15

Saccharin sodium 0.07 Mouthwash

ACTMP 193 ® (lupine peptides) 2.00

Cremophor RH40 ® 0.30 Glycerin 15

Saccharin sodium 0.03

Soluble extract of avocado sugars 1.00

EUCA MLNT Aroma 0.08

POBM 0.20 Potassium sorbate 0.50

Water QSP 100

Claims

1. Use of a composition comprising D-mannoheptulose and or perseitol and a suitable pharmaceutically acceptable excipient, for the manufacture of a medicament or a veterinary composition intended for the treatment and / or prevention of diseases linked to a modification of innate and / or acquired immunity by increasing the production of antimicrobial peptides, of the family of cathelicidines and / or beta-defensin, advantageously hBD-2.

2. Use of a composition comprising D-mannoheptulose and / or perseitol and a suitable pharmaceutically acceptable excipient, for the manufacture of a medicament or a veterinary composition intended for the treatment and / or prevention of diseases linked to a change in innate and or acquired immunity by stimulation of anti-microbial like peptides, such as a specific elastase inhibitor, particularly elfin (SKALP).

3. Use according to claim 1 or 2, characterized in that said diseases are linked to the presence of microorganisms such as Gram + and or Gram- bacteria, fungi, yeasts or viruses.

4. Use according to any one of the preceding claims, characterized in that said diseases are chosen from the group consisting of: - infections of the skin and appendages, in particular chosen from the group consisting of folliculitis, dandruff, l 'hyper-seborrhea, boil, abscess, impetigo or panaris; - inflammatory dermatoses, such as atopic dermatitis, contact and / or atopic eczema, psoriasis, acne, irritant dermatitis; - diseases associated with a change in the Thl / Th2 balance; - diseases associated with a change in the synthesis of cytokines, such as IL-4 and / or 1TL-13; or - burns.

5. Use according to any one of claims 1 to 3, characterized in that said diseases are pathologies related to a deficit of the skin barrier, such as hyper-reactive, atopic, dry or aged skin, or related pathologies to skin weakened by environmental aggression.

6. Use according to any one of the preceding claims, characterized in that the medicament is suitable for the protection of the skin: - healthy immature infants or children; - immature pathologies of infants or children; or - healthy or pathological in adult or elderly individuals.

7. Use according to any one of claims 1 to 5, characterized in that the medicament is intended to promote healing, in normal or pathological healing processes, such as ulcers and bedsores.

8. Use according to any one of claims 1 to 5, characterized in that the medicament is intended to treat and / or prevent periodontal diseases.

9. Use according to any one of claims 1 to 5, characterized in that the medicament is intended to treat and / or prevent inflammatory joint pathologies such as osteoarthritis.

10. Use according to any one of claims 1 to 5, characterized in that the medicament is intended to treat and / or prevent infections of the mucous membranes, in particular of the vaginal, intestinal, respiratory, nasal or atrial mucous membranes.

11. Use according to any one of claims 1 to 5, characterized in that the medicament is intended to treat and / or prevent infections of the ocular system.

12. Use according to any one of the preceding claims, characterized in that the composition comprises 0.001 to 30%> by weight of D-mannoheptulose, by relative to the total weight of said composition, and / or 0.001 to 30% by weight of perseitol, relative to the total weight of said composition.

13. Use according to any one of the preceding claims, characterized in that the source of D-mannoheptulose and / or perseitol is a water-soluble extract of avocado sugars, advantageously capable of being obtained by a process comprising the successive stages following: - obtaining an avocado cake, advantageously from the avocado fruit, by drying the avocado then extracting the lipids; then - cryogenic grinding and complete delipidation of said cake, then decantation and centrifugation in order to recover a soluble fraction rich in C7 sugars (elimination of the cake); - demineralization on ionic resin of said soluble fraction, obtained in the previous step; then - ultrafiltration at 10,000 daltons; and - vacuum concentration and packaging.

14. Use according to claim 13, characterized in that the water-soluble extract of avocado sugars comprises by weight, relative to the total weight of the dry matter of the extract (relative composition determined by HPLC): - D-mannoheptulose 5 to 80%> - Perseitol 5 to 80% - Sucrose less than 10%> - Glucose less than 10%> - Fructose less than 10%.

15. Use according to any one of the preceding claims, characterized in that the composition also comprises an avocado peptide extract, in particular an avocado peptide extract which comprises 2 to 10%> by weight of alpha-amino nitrogen , relative to the weight of the dry matter of the peptide extract.

16. A medicament comprising 0.001 to 30% by weight, relative to the total weight of the drug D-mannoheptulose, 0.001 to 30%> by weight, relative to the total weight of the medicament of perseitol and an appropriate pharmaceutically acceptable excipient.

17. Cosmetic or nutraceutical composition comprising 0.001 to 30%> by weight of D-mannoheptulose, relative to the total weight of said composition, and 0.001 to 30%> by weight of perseitol, relative to the total weight of said composition and vice versa suitable cosmetically acceptable or food excipient.

18. Cosmetic or nutraceutical composition according to claim 17, further comprising an avocado peptide extract.

19. Cosmetic treatment method for sensitive, irritated, allergic, dry, aged, intolerant skin and or mucous membranes, having a cutaneous barrier disorder, weakened by an environmental attack presenting redness of the skin or having a non-pathological immunological imbalance, characterized in that it consists in applying to the skin and / or the mucous membranes a cosmetic composition according to claim 17 or 18.